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Details

Stereochemistry ACHIRAL
Molecular Formula C13H18Br2N2O.C9H10N4O4
Molecular Weight 616.303
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMBROXOL ACEFYLLINATE

SMILES

CN1C2=C(N(CC(O)=O)C=N2)C(=O)N(C)C1=O.NC3=C(CN[C@H]4CC[C@H](O)CC4)C=C(Br)C=C3Br

InChI

InChIKey=IPUHJDQWESJTGD-PFWPSKEQSA-N
InChI=1S/C13H18Br2N2O.C9H10N4O4/c14-9-5-8(13(16)12(15)6-9)7-17-10-1-3-11(18)4-2-10;1-11-7-6(8(16)12(2)9(11)17)13(4-10-7)3-5(14)15/h5-6,10-11,17-18H,1-4,7,16H2;4H,3H2,1-2H3,(H,14,15)/t10-,11-;

HIDE SMILES / InChI

Molecular Formula C13H18Br2N2O
Molecular Weight 378.103
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C9H10N4O4
Molecular Weight 238.2001
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Ambroxol, a substituted benzylamine, is an active metabolite of bromhexine, which is itself a synthetic derivative of vasicine, the active principle extracted from the plant species Adhatoda vasica. Ambroxol is an expectorant exerting mucokinetic properties, mucociliary activity, stimulation of surfactant production, anti-inflammatory and antioxidative actions and the local anaesthetic effect. Ambroxol was discovered at and has been manufactured by Dr. Karl Thomae GmbH, a division of Boehringer Ingelheim. The ambroxol patent is expired and the drug is available as a generic product from many different companies. Ambroxol was originally developed by Boehringer Ingelheim as a OTC therapy for respiratory disorders related to excessive mucus. Ambroxol's indication is secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport. Boehringer Ingelheim markets the product under various brand names such as Mucosolvan® and Lasolvan®. Ambroxol was identified and found to be a pH-dependent, mixed-type inhibitor of glucocerebrosidase (GCase). Its inhibitory activity was maximal at neutral pH, found in the endoplasmic reticulum, and undetectable at the acidic pH of lysosomes. The pH dependence of Ambroxol to bind and stabilize the enzyme was confirmed. Ambroxol increases both the lysosomal fraction and the enzymatic activity of several mutant GCase variants. This profile of Ambroxol would allow to bind and stabilize GCase in the endoplasmic reticulum (thus preventing its degradation within endoplasmic reticulum), but without affecting GCase in the lysosomes (thus allowing it to degrade glucosylceramide). Indeed, studies showed that Ambroxol treatment significantly increased N370S and F213I mutant GCase activity and protein levels in fibroblasts originally obtained from Gaucher patients. Gaucher's disease is caused by the deficiency of glucocerebrosidase; ambroxol is a chaperone that acts by binding to and stabilising glucocerebrosidase. Zywie (formerly ExSAR Corporation) and Belrose Pharma are developing ambroxol hydrochloride (BEL 0218) for the treatment of type III Gaucher's disease. .

CNS Activity

Approval Year

PubMed

PubMed

TitleDatePubMed
Neltenexine tablets in smoking and non-smoking patients with COPD. A double-blind, randomised, controlled study versus placebo.
2001 Aug
The predictive value of asthma medications to identify individuals with asthma--a study in German general practices.
2001 Nov
[Lipoid pneumonia following attempted suicide by intravenous injection of lamp oil].
2001 Nov 15
[Effect of ambroxol on lipid peroxidation in homogenates of the human placenta].
2001 Oct
[The effect of inhaled ambroxol treatment on clinical symptoms and chosen parameters of ventilation in patients with exacerbation of chronic obstructive pulmonary disease patients].
2001 Sep
Enhanced resistance to Sendai virus infection in DBA/2J mice with a botanical drug combination (Sinupret).
2001 Sep
Immunoassay screening of lysergic acid diethylamide (LSD) and its confirmation by HPLC and fluorescence detection following LSD ImmunElute extraction.
2002 Apr
Depressant effect of ambroxol on stimulated functional responses and cell death in rat alveolar macrophages exposed to silica in vitro.
2002 Feb
Ambroxol inhibits platelet-derived growth factor production in human monocytic cells.
2002 Feb 1
Adenosine increases human platelet levels of cGMP through nitric oxide: possible role in its antiaggregating effect.
2002 Jan 1
Determination of ambroxol in human plasma using LC-MS/MS.
2003 Jun 1
Nutritional supplements and infection in the elderly: why do the findings conflict?
2006 Nov 23
Proteases essential for human influenza virus entry into cells and their inhibitors as potential therapeutic agents.
2007
In situ gelling pectin formulations for oral drug delivery at high gastric pH.
2007 Apr 20
Post-marketing assessment of content and efficacy of preservatives in artemisinin-derived antimalarial dry suspensions for paediatric use.
2007 Jan 26
Simultaneous determination and pharmacokinetic study of roxithromycin and ambroxol hydrochloride in human plasma by LC-MS/MS.
2007 Jul
Determination of ambroxol in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI).
2007 Jun 15
[Determination of ambroxol and clenbuterol in human plasma by LC-MS/MS method].
2007 Mar
Parenteral ambroxol treatment causes xanthine and calcium oxalate stones in rats.
2007 May
Solid-state chemistry of ambroxol theophylline-7-acetate.
2007 May
Action of neltenexine on anion secretion in human airway epithelia.
2007 May 18
Patents

Sample Use Guides

In Vivo Use Guide
Adults: daily dose of 30 mg (one Ambroxol tablet ) to 120 mg (4 Ambroxol tablets) taken in 2 to 3 divided doses Children up to 2 years: half a teaspoonful Ambroxol syrup twice daily Children 2 - 5 years: half a teaspoonful Ambroxol syrup 3 times daily Children over 5 years: One teaspoonful Ambroxol syrup 2-3 times daily.
Route of Administration: Oral
In Vitro Use Guide
Ambroxol exerted a biphasic response in surfactant secretion, with a significant increase at low concentrations (1 - 10 uM) and an inhibition at high concentrations (≥ 0.1 mM), which is beyond reported plasma Ambroxol concentrations in blood
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:28:50 UTC 2019
Edited
by admin
on Mon Oct 21 23:28:50 UTC 2019
Record UNII
0HM1E174TN
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMBROXOL ACEFYLLINATE
MART.   WHO-DD  
Common Name English
ACEBROPHYLLINE
Common Name English
AMBROMUCIL
Common Name English
AMBROXOL ACEFYLLINATE [WHO-DD]
Common Name English
7H-PURINE-7-ACETIC ACID, 1,2,3,6-TETRAHYDRO-1,3-DIMETHYL-2,6-DIOXO-, COMPD. WITH TRANS-4-(((2-AMINO-3,5-DIBROMOPHENYL)METHYL)AMINO)CYCLOHEXANOL (1:1)
Systematic Name English
BRONCOMNES
Common Name English
SURFOLASE
Common Name English
CYCLOHEXANOL, 4-(((2-AMINO-3,5-DIBROMOPHENYL)METHYL)AMINO)-, TRANS-, MONO(1,2,3,6-TETRAHYDRO-1,3-DIMETHYL-2,6-DIOXO-7H-PURINE-7-ACETATE) (SALT)
Systematic Name English
AMBROXOL ACEFYLLINATE [MART.]
Common Name English
AMBROXOL-THEOPHYLLINE-7-ACETATE
Common Name English
Code System Code Type Description
RXCUI
186010
Created by admin on Mon Oct 21 23:28:50 UTC 2019 , Edited by admin on Mon Oct 21 23:28:50 UTC 2019
ALTERNATIVE
RXCUI
236595
Created by admin on Mon Oct 21 23:28:50 UTC 2019 , Edited by admin on Mon Oct 21 23:28:50 UTC 2019
PRIMARY RxNorm
CAS
96989-76-3
Created by admin on Mon Oct 21 23:28:50 UTC 2019 , Edited by admin on Mon Oct 21 23:28:50 UTC 2019
PRIMARY
EVMPD
SUB12842MIG
Created by admin on Mon Oct 21 23:28:50 UTC 2019 , Edited by admin on Mon Oct 21 23:28:50 UTC 2019
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY